The present invention relates to devices used in percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA) procedures, particularly when adapted for the dilatation of intravascular tissue and the localized delivery of a therapeutic agent to the dilatated tissue.
PTA and PTCA procedures have gained widespread acceptance in the treatment of vascular constrictions and blockages, and are increasingly favored because they involve less trauma and lower cost compared to traditional alternative procedures such as coronary bypass. However, the recurrence of total or partial blockage, usually from three to six months after the procedure, continues to be of concern. This phenomenon, known as restenosis, appears in about thirty percent or more of the cases that originally appear successful. Restenosis can present a risk to the patient and typically necessitates another tissue dilatation, or an alternative procedure.
Certain therapeutic agents can be administered to reduce restenosis, e.g. anti-thrombolitic agents such as heparin to prevent clotting, and anti-proliferative agents such as dexamethasone to prevent smooth muscle cell migration and proliferation. Catheters have been developed for local delivery of therapeutic agents. For example, U.S. Pat. No. 5,087,244 (Wolinsky) discloses a catheter with a substantially inelastic distal balloon with a plurality of minute (e.g. 25 micrometer) perforations said to provide a low, weeping flow rate of a liquid to the surrounding tissue. Another approach to localized delivery involves inflating spaced apart proximal and distal balloons against arterial walls to provide a chamber about a treatment site, then delivering an agent into the chamber, e.g. as disclosed in U.S. Pat. No. 4,824,436 (Wolinsky).
Several devices have been developed to perform both the dilatation and drug delivery functions. Examples include U.S. Pat. No. 5,415,636 (Forman), assigned to the assignee of this application, featuring a catheter with a dilatation balloon and a pair of occlusion balloons, one proximal and one distal with respect to a drug delivery port. U.S. Pat. No. 4,994,033 (Schockey), also assigned to the present assignee, discloses an intravascular dilation and delivery catheter with inner and outer hollow expansible sleeves at the distal ends of three concentric catheters. The outer sleeve includes minute openings through which a liquid dispersant perfuses as the inner sleeve is expanded.
U.S. Pat. No. 5,049,132 (Shaffer) discloses a two-balloon catheter in which the outer balloon includes apertures sized to permit flow of a liquid through the balloon to treat tissue, and in which the outer balloon is spot-sealed to an inner balloon in several areas spaced from the ends of the balloons. In U.S. Pat. No. 5,421,826 (Crocker) a drug delivery balloon with perforations is disposed concentrically about a dilatation balloon, with the two balloons preferably heat sealed together at the proximal and distal ends. The dilatation balloon is used to expel the drug out of the drug delivery balloon, and pulls the delivery balloon with it when aspirated, to minimize external dimensions.
The aforementioned approaches have proven useful in certain circumstances. However, the growing interest in gene therapy for treating cardiovascular diseases including restenosis, and the nature of coronary arteries, raise challenges not yet adequately addressed.
More particularly, gene therapy involves large, complex molecules that tend to rapidly combine with proteins in the bloodstream to lose their efficacy. This raises a need to protect gene therapy agents from contact with the blood as they are maintained in contact with a vessel wall under treatment. Similarly, a freshly cracked lesion can be more effectively medicated if it is protected from contact with blood during treatment.
Coronary vasculature includes many collateral arteries and branches in which the conventional two-balloon approach does not effectively block or divert the flow of blood, nor do the conventional non-distensible dilatation and drug delivery balloons establish a conforming contact with the arterial wall at low pressures.
Therefore, it is an object of the present invention to provide a drug delivery device for effectively maintaining a therapeutic agent in contact with vessel walls while protecting the vessel walls and the agent from contact with blood.
Another object is to provide a combination tissue dilatation and drug delivery device that facilitates substantially immediate treatment of a freshly cracked lesion while protecting the lesion from contact with blood.
A further object is to provide a process for treating vascular tissue including expanding a liquid permeable sheath elastically into intimate and substantially conforming contact with the vascular tissue, and causing a therapeutic agent to pass through the sheath to the surrounding tissue while the sheath remains expanded.
Yet another object is to provide a dilatation and drug delivery device in which a therapeutic agent is administered after tissue dilatation and at a pressure and flow rate determined independently of the tissue dilatation means.
To achieve the above and other objects, there is provided a body insertable treatment device. The device includes an elongate delivery member having a proximal end region and a distal end region. The delivery member is maneuverable transluminally to position the distal end region at a treatment site within the body lumen. The device has a treatment fluid delivery means including a sheath mounted to the delivery member along the distal end region. The sheath is elastically expandable radially into a substantially conforming contact with surrounding tissue at the treatment site. While expanded, the sheath provides a compartment for containing at treatment fluid. The sheath further is adapted to allow passage of the treatment fluid from within the compartment to the surrounding tissue during such contact. The treatment fluid delivery means further includes a means for supplying the treatment fluid under pressure to the compartment to expand the sheath radially into the conforming contact, to maintain such contact, and to provide the treatment fluid for such passage of the treatment fluid. A tissue dilatation means is mounted to the delivery member and disposed within the compartment. The tissue dilatation means is enlargeable to act radially upon the surrounding tissue through the sheath and thereby effect a dilatation of the surrounding tissue. The dilatation means and the sheath are mounted to the delivery member independent from one another to allow radial expansion of the sheath into the conforming contact without radially enlarging the dilatation means, and to allow radial contraction of dilatation means while maintaining the sheath in such contact.
Preferably the delivery means comprises an elongate and flexible catheter, with the dilatation means comprising a substantially inelastic and fluid impermeable dilatation balloon. The catheter has at least two lumens, one fluidly coupled to the dilatation balloon for supplying a fluid under pressure to the dilatation chamber, and the other open to the compartment for supplying the treatment fluid under pressure to expand the sheath and provide the desired treatment. A third lumen can run substantially the length of the catheter, to accommodate a guidewire.
The sheath advantageously is formed of a biocompatible elastomer having a modulus of elasticity in the range of about 2,000 to 80,000 psi, and with a uniform thickness in the range of about 0.5-5 mils. Accordingly, responsive to a low inflation pressure (e.g. about one atmosphere gauge pressure), the sheath readily expands into the desired intimate and conforming contact with tissue. The elasticity is a positive factor in permitting the sheath to stretch in response to encountering tissue surface irregularities.
The sheath material can be either fluid impervious or naturally porous. In the former case, pores are formed through the material with a size, number and arrangement as desired. In the latter case, the material is selected with the desired pore size in mind. Some of the porous materials (e.g. collagen) lack the elasticity just discussed, yet provide the necessary conforming contact if kept sufficiently thin, e.g. at most about 2 mils in thickness.
Several advantages arise from the conforming contact of the sheath against vascular tissue. The first is an improved fluid seal that more effectively prevents blood from flowing between the expanded sheath and the surrounding tissue. This protects the tissue from exposure to blood, while also protecting a therapeutic agent from such exposure during its administration. If extended treatment is contemplated, the catheter can include a perfusion lumen enabling blood to flow past the treatment area without contacting tissue under treatment.
A further advantage is a more uniform administration of the therapeutic agent. Regardless of whether the sheath is formed of a porous material, or a substantially fluid impervious material in which multiple pores are formed, improved uniformity of application results from the more intimate and more conforming surface contact. Crevices, folds and other recessive tissue irregularities are more likely to receive the therapeutic agent.
The device is particularly effective as part of a treatment system that further includes a control means to govern a first fluid pressure at which the treatment fluid is provided to the compartment, a second control means to govern a second fluid pressure at which dilatation fluid is provided to the dilatation balloon, and further includes a guidewire adapted for intravascular insertion to position a distal end of the guidewire near the treatment site and a proximal end for receipt into a distal end of the guidewire lumen, to facilitate a distal advance of the catheter over the guidewire toward the treatment site.
The system can be employed in a process for treating tissue within a body lumen, according to the following steps:
a. distally intraluminally advancing an elongate flexible catheter until a flexible sheath mounted to a distal end of the catheter is aligned with a predetermined treatment site;
b. supplying a treatment fluid under pressure to a compartment formed by the sheath, (i) to elastically expand the sheath radially into an intimate and substantially conforming contact with surrounding tissue at the treatment site, (ii) to cause the treatment fluid to pass through the sheath from the compartment to the surrounding tissue, and (iii) to maintain the sheath expanded into such contact.
The process further can include the following additional steps:
c. while maintaining the sheath in such contact, radially expanding a tissue dilatation means within the compartment until the dilatation means engages the sheath, then further radially expanding the dilatation means whereby the dilatation means acts radially upon the surrounding tissue through the sheath to effect a dilatation of the surrounding tissue;
d. following the dilatation, radially contracting the dilatation means and simultaneously maintaining the sheath in such contact to administer the treatment fluid to the dilatated tissue; and
e. following said administering of the treatment fluid, discontinuing the supply of the treatment fluid to allow the sheath to radially contract under a residual elastic force.
Because the sheath is maintained in contact with tissue during dilatation, freshly created tissue surfaces are protected from contact with blood. Radial contraction of the dilatation means while maintaining the sheath in contact with tissue ensures that administration of the therapeutic agent occurs at a suitably low pressure, free from any influence due to the higher pressures characteristic of tissue dilatation balloons (e.g. 12-15 atmospheres). Thus, the present arrangement avoids two problems of prior devices that depend on dilatation balloon inflation for xe2x80x9csqueezablyxe2x80x9d delivering drugs: (1) the tendency in irregular vessel profiles for the dilatation balloon to contact radially inward parts of the drug delivery balloon, to the point of closing off some of the drug delivery pores; and (2) unwanted pressure gradients in the treatment fluid, due to episodes and near episodes of such contact. Consequently the present arrangement affords a more uniform delivery and better control over the pressure and flow rate of the therapeutic agent.
Thus in accordance with the present invention, the likelihood of restenosis is significantly reduced due to administration of therapeutic agents through an elastic membrane held in intimate, conforming contact with the tissue under treatment. The agent is effectively concentrated at the treatment area, with little or no loss into the bloodstream and virtually no contact with blood. At the same time the tissue is protected from contact with blood during treatment.